Eugenia jambolana is a medicinal plant traditionally used for treating diabetes. The bioactive compound FIIc, which is derived from the fruit pulp of E. jambolana, has been identified and purified as α-HSA. Previous studies have demonstrated that administration of α-HSA for 6 weeks improved glycemic index and dyslipidemia in rats with T2D. This study investigated the molecular mechanism underlying the potential therapeutic effects of α-HSA in experimentally induced diabetic rats. Male Wistar rats were divided into four groups: diabetic control, diabetic treated with FIIc, diabetic treated with α-HSA, and diabetic treated with glibenclamide. Over a 6-week experimental period, transcriptomic analysis was conducted on liver, skeletal, and pancreatic tissue samples collected from the rats. The study findings revealed significant upregulation of genes associated with glucose metabolism and insulin signaling in the groups treated with FIIc and α-HSA, compared to the diabetic control group. Moreover, pro-inflammatory genes were downregulated in these treatment groups. These results indicate that α-HSA has the potential to modulate key metabolic pathways, improve glucose homeostasis, enhance insulin sensitivity, and alleviate inflammation. This study provides compelling scientific evidence supporting the potential of α-HSA as a therapeutic agent for diabetes treatment. The observed upregulation of genes related to glucose metabolism and insulin signaling, along with the downregulation of pro-inflammatory genes, aligns with the pharmacological activity of α-HSA in controlling glucose homeostasis and improving insulin sensitivity. These findings suggest that α-HSA holds promise as a novel therapeutic approach for managing diabetes and its associated complications.